|Year : 2014 | Volume
| Issue : 3 | Page : 393-399
Comparative study of the effect of adding two different doses of dexmedetomidine to levobupivacaine/hyaluronidase mixture on the peribulbar block in vitreoretinal surgery
Hala S El-Ozairy, Ayman I Tharwat
Department of Anesthesiology, Intensive Care, and Pain Management, Faculty of Medicine, Ain-Shams University, Cairo, Egypt
|Date of Web Publication||27-Aug-2014|
Hala S El-Ozairy
Department of anesthesiology, Intensive Care, and Pain Management, Faculty of Medicine, Ain-Shams University, Cairo
Source of Support: None, Conflict of Interest: None
Many additives have been added to local anesthetics in PBA to decrease the time of onset and increase the duration of analgesia to suit the relatively long vitreoretinal surgery with limited success. Dexmedetomidine has been added to local anesthetics for such purpose.
Patients and methods
Sixty consented ASA I-II adult patients undergoing vitreoretinal surgery were enrolled in this randomized, double blind, controlled study. Patients were randomly and evenly assigned to three groups to receive one of three anesthetic solutions for PBA: group C, group D25, and group D50. Patients in group C received 6 ml of 0.5% levobupivacaine with 10 IU/ml hyaluronidase in addition to 1 ml of normal saline. Patients in groups D25 and D50 received the same mixture but with replacement of the normal saline with 25 and 50 mcg dexmedetomidine, respectively. Intraoperative recordings included onset and duration of corneal anesthesia and globe akinesia, hemodynamics, intraocular pressure (IOP), and Ramsay sedation score. Postoperative recordings included time to first rescue analgesia and number of doses required, pain score, and patient and surgeon satisfaction score.
The onset of corneal anesthesia and globe akinesia was significantly shorter in group D50 than in group C (1.05 ± 0.50 and 6.90 ± 1.94 vs. 1.68 ± 0.78 and 9.10 ± 2.14); in group D25 the onset was insignificantly shorter. Duration of anesthesia was significantly longer in both groups compared with control, as was the time to first rescue analgesia. IOP was also significantly lower in both groups compared with control.
Addition of two different doses of dexmedetomidine (25 and 50 mcg) to levobupivacaine/hyaluronidase mixture shortened the onset and prolonged the duration of peribulbar block in patients undergoing vitreoretinal surgery. It also lowered the IOP and provided sedation with patient's cooperation, leading to better patient and surgeon satisfaction.
Keywords: dexmedetomidine, levobupivacaine, peribulbar anesthesia, vitreoretinal surgery
|How to cite this article:|
El-Ozairy HS, Tharwat AI. Comparative study of the effect of adding two different doses of dexmedetomidine to levobupivacaine/hyaluronidase mixture on the peribulbar block in vitreoretinal surgery. Ain-Shams J Anaesthesiol 2014;7:393-9
|How to cite this URL:|
El-Ozairy HS, Tharwat AI. Comparative study of the effect of adding two different doses of dexmedetomidine to levobupivacaine/hyaluronidase mixture on the peribulbar block in vitreoretinal surgery. Ain-Shams J Anaesthesiol [serial online] 2014 [cited 2019 May 24];7:393-9. Available from: http://www.asja.eg.net/text.asp?2014/7/3/393/139576
Levobupivacaine, levorotatory isomer of the racemic mixture of bupivacaine, was introduced into clinical practice in the last few years . It has been used at all sites, including peribulbar and retrobulbar blockade . The doses used are very similar to those of bupivacaine, with many advantages: lower arrhythmogenic potential, lesser inotropic effect on the cardiac muscle, and less depressing action on the central nervous system .
Although peribulbar block is the preferred option for many ophthalmic surgeons, there is reluctance to use it alone for vitreoretinal surgery. This may stem from the longer, more unpredictable, and uncomfortable nature of such surgery . Surgical dissatisfaction because of insufficient akinesia resulting from partial blockade  and patient discomfort during prolonged surgery is another limitation. Many additives were added to local anesthetics to decrease the time of onset of action and increase the duration of analgesia with limited success - for example, clonidine, hyaluronidase, sodium bicarbonate, and adrenaline [6-10].
Dexmedetomidine is a centrally acting, highly specific α2 -agonist that has been used as an additive to local anesthetics in peripheral nerve block, brachial plexus block , and subarachnoid anesthesia to shorten the onset and prolong the duration of analgesia.
The primary endpoint of this study is to evaluate the efficacy of two different doses of dexmedetomidine added to levobupivacaine/hyaluronidase mixture for peribulbar anesthesia in decreasing the time of onset and prolonging the duration of the block.
| Patients and methods|| |
After obtaining local medical ethics committee approval and written informed consent, 60 ASA I-II patients scheduled for elective vitreoretinal surgery with anticipated surgery time 2-3 h were enrolled in this prospective, randomized, double blind controlled study. The study was carried out at Ain Shams University Hospitals in the period between September 2012 and April 2013. All patients were between 18 and 65 years of age.
Exclusion criteria included known allergy to any of the study drugs, significant cardiovascular disease (second-degree or third-degree heart block, heart failure, or symptomatic coronary artery disease), uncontrolled hypertension, retrobulbar hemorrhage, coagulopathy or anticoagulation therapy, hepatic dysfunction, mental illness, chronic alcohol abuse or drug addiction, pregnancy, and any contraindication to PBA. Procedures lasting more than 3 h or less than 2 h were also excluded from the study.
On arrival at the OR, standard monitoring was applied, including five-lead ECG, noninvasive blood pressure monitoring, heart rate monitoring, and pulse oximetry. Baseline intraocular pressure (IOP) was measured in both eyes after applying topical anesthesia with 0.5% tetracaine hydrochloride drops using a Tono-Pen XL hand-held tonometer (Mentor, Norwell, Massachusetts, USA).
Patients were randomized using a computer-generated list into three groups of 20 patients each to receive one of three anesthetic solutions for PBA: group C, group D25, and group D50. Patients in group C received 6 ml of 0.5% levobupivacaine and 10 IU/ml hyaluronidase (60 IU in 1 ml sterile water) in addition to 1 ml of normal saline. Patients in group D25 received 6 ml of levobupivacaine and 10 IU/ml of 0.5% hyaluronidase in addition to 25 mcg of dexmedetomidine (25 mcg in 1 ml saline). Patients in group D50 received 6 ml of 0.5% levobupivacaine and 10 IU/ml hyaluronidase in addition to 50 mcg of dexmedetomidine (50 mcg in 1 ml saline).
Anesthesiologists not participating in the study prepared all medications.
Local anesthesia was induced in the form of peribulbar block with two injections by an anesthesiologist blinded to the study solution using a 23 G, 25 mm beveled needle. The first injection was given transcutaneously at the junction between the outer third and medial two-thirds of the inferior orbital margin. The volume injected in this approach was 3-4 ml, discontinuing the injection when 'lead fullness' appeared. The second injection was at the medial canthal episcleral, and involved injecting a volume of 2-3 ml and discontinuing injection when subconjunctival edema and/or 'orbital fullness appeared'. Before each injection, aspiration was performed to exclude intravascular needle placement.
Intermittent compression was performed for 5-10 min using a Honan balloon set at 30 mmHg. Ocular akinesia was assessed every 2 min in four directions using a three-point scale for evaluating: (0) complete motor block for the direction examined; (1) 50% movement; and (2) full eye movement (total score 0-8) . IOP was measured at 1, 5, and 10 min after injection. Corneal sensation was evaluated using a cotton wick every 30 s until the onset of anesthesia and then every 15 min until recovery.
The patients were asked to forcefully close their eyes to assess the orbicularis muscle on a scale of 0-2 (0 = complete akinesia, 1 = partial movement, 2 = pronounced movement) .
Time taken for the achievement of adequate conditions to start the surgery (defined as the presence of corneal anesthesia together with an ocular movement score ͳ1 and eyelid squeezing score of 0) was recorded.
If adequate conditions to begin surgery were not obtained 10 min after performing the block, supplemental injection with 2 ml of 2% lidocaine either inferotemporally or medially was administered based on the anesthesiologist's assessment. These patients were excluded from the study. It was decided that if the patient became restless during the surgery, general anesthesia would be induced and the patient excluded from the study. If the patient required supplement anesthesia intraoperatively, subtenon injection would be given by the surgeon and the patient excluded.
Sedation levels were assessed with a modified Ramsay sedation scale (1, anxious and agitated or restless, or both; 2, cooperative, oriented, and tranquil; 3, responds to commands only; 4, brisk response to light glabellar tap or loud auditory stimulus; 5, no response to light glabellar tap or loud auditory stimulus) every 15 min during the first 60 min of surgery and then every 30 min until the end of surgery and for the first 2 h thereafter.
Intraoperatively, all patients received nasal oxygen throughout the procedure and were continuously monitored for blood pressure, heart rate, and oxygen saturation, which were recorded every 15 min during the first 60 min of surgery and then every 30 min until the end of surgery and for the first 2 h thereafter. If systolic blood pressure decreased by more than 20% of baseline, 5 mg intravenous ephedrine was injected incrementally. Bradycardia, defined as HR less than 60 beats/min, was treated with 10 mcg/kg atropine intravenously.
Postoperatively, both the surgeon and the patients were asked to assess their satisfaction on a five-point Likert scale, where 5 indicated quite satisfied, 4 indicated satisfied, 3 indicated neutral, 2 indicated unsatisfied, and 1 indicated quite unsatisfied.
The duration of sensory and motor block was assessed by onset of pain and recovery of eyeball movement, respectively. On the first postoperative day, the following variables were recorded: degree of pain (using a five-point verbal rating score: 0, no pain; 1, mild pain; 2, moderate pain; 3, severe pain; and 4, unbearable pain). Pain was assessed at the end of surgery and every 60 min up to 2 h and then at 6 h and 24 h. Paracetamol tablets (500 mg) were given if the verbal rating score was 2 or higher. The time to first request for analgesic and the total analgesic requirement in 24 h were recorded.
Statistical analysis was carried out using the statistical package for social sciences version 17 (SPSS Inc., Chicago, Illinois, USA). It was estimated that a sample of 19 patients per group would have a power of 85% to detect a large effect size (Ͷ) of 0.45 as regards the primary outcome measures (i.e. onset and duration of corneal anesthesia and globe akinesia).
The Shapiro - Wilk test was used to examine the normality of numerical variables. Numerical variables were presented as mean ± SD or as median and interquartile range, whereas error bars represent 95% confidence interval. Categorical variables were presented as ratio or as number and percentage. One-way analysis of variance was used for intergroup comparisons as regards normally distributed variables. The Tukey test was used for post-hoc pairwise comparisons. For non-normally distributed variables, the Kruskal - Wallis test was used with application of the Mann - Whitney U-test for post-hoc comparisons. Bonferroni's correction of the level of significance was used to correct for multiple comparisons.
The Pearson χ2 -test was used to compare categorical variables. For multiple post-hoc comparisons with the U-test, P-values less than 0.017 were regarded as statistically significant. For other comparisons, a conventional P-value less than 0.05 was considered statistically significant.
| Results|| |
A total of 60 patients were randomly and evenly enrolled in this study. One patient was excluded from group C as the patient became restless during surgery and general anesthesia was induced. One patient was excluded from group D50 because the surgical time exceeded 3 h. None of the blocks failed or needed supplemental injection.
Patients' characteristics were comparable among the three groups [Table 1], as well as the duration of surgery [Table 2].
The onset of corneal anesthesia [Table 2] was significantly shorter in group D50 than in group C (1.05 ± 0.50 vs. 1.68 ± 0.78; P = 0.018). The onset of corneal anesthesia in group D25 was shorter than in the control group; however, this was found to be statistically insignificant (1.35 ± 0.58 vs. 1.68 ± 0.78).
Onset of globe akinesia [Table 2] was found to be nonsignificantly shorter in group D25 than in group C (8.13 ± 2.10 vs. 9.10 ± 2.14), but it was significantly shorter in group D50 (6.90 ± 1.94; P = 0.022).
The duration of corneal anesthesia [Table 2] was significantly higher in group D50 compared with groups D25 and C (390.40 ± 10.31 compared with 164.41 ± 13.80 and 154.33 ± 17.34, respectively; P < 0.001).
The duration of globe akinesia was significantly higher in groups D25 and D50 compared with group C (197.30 ± 25.95, 283.10 ± 26.40, and 154.33 ± 17.34, respectively; P < 0.001) [Table 2].
There was no statistically significant difference in the mean HR among the three groups, although it was slightly lower in groups D25 and D50 than in the control group during the first 30 min after the block [Figure 1].
Mean arterial blood pressure [Figure 2] was significantly lower in group D25 compared with group C at 15 min (74 ± 8 and 85 ± 8.5). In group D50 the mean arterial blood pressure was found to be significantly lower than in the control group during the first 60 min. However, none of the patients received ephedrine. No episodes of hypoxia or respiratory depression were reported.
|Figure 2: Mean arterial blood pressure (MAP). *Signifi cantly higher than in group D25 and group D50. †Signifi cantly higher than in group D50.|
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Baseline IOP was comparable among the three groups. However, IOP was found to be significantly lower in groups D25 and D50 compared with the control group at 1, 5, and 10 min after injection with a P-value of less than 0.001 [Figure 3].
|Figure 3: Intraocular pressure (IOP). †Signifi cantly higher than in group D25 and group D50.|
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The mean Ramsay sedation score (RSS) was found to be significantly higher in groups D25 and D50 than in the control group at 15, 30, 45, and 60 min after injection [Figure 4]. RSS was also significantly higher in group D50 than in group D25 at 45 and 60 min after injection (P < 0.05).
|Figure 4: Ramsay sedation score. *P < 0.05 group D25 versus group C; **P < 0.01 group D50 versus group C. †P < 0.05 group D25 versus group C; ‡P < 0.01 group D25 versus group C. ††P < 0.01 group D50 versus group C; ‡‡P < 0.01 group D50 versus group C. ††,*P < 0.05 group D50 versus group D25; ‡‡,*P < 0.05 group D50 versus group D25|
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The time to first rescue analgesia was found to be significantly longer in groups D25 and D50 compared with group C (264.2 ± 75.06, 346.1 ± 81.05, and 190 ± 49.3, respectively) [Table 3]. The number of patients not requiring analgesia was higher in groups D25 and D50 compared with the control group; however, the difference was found to be insignificant [13 (65%), 16 (84.2%), and 11 (57.9%), respectively; P = 0.464]. The number of patients with no pain was also found to be nonsignificantly higher in groups D25 and D50 compared with the control group [17 (85%), 18 (94.7%), and 11 (57.9%), respectively; P = 0.071].
Although the number of satisfied patients and surgeons was higher in groups D25 and D50 compared with the control group, this was found to be statistically nonsignificant (P = 0.038 and 0.413, respectively) [Table 4].
| Discussion|| |
The main finding in this study was that the addition of two different doses of dexmedetomidine (25-50 mcg) to levobupivacaine-hyaluronidase mixture shortened the onset and prolonged the duration of peribulbar block in patients undergoing vitreoretinal surgery. Furthermore, the addition of dexmedetomidine prevented the increase in IOP following PBA and led to better patient and surgeon satisfaction.
In a similar study conducted by Channabasappa et al.  on 90 patients undergoing elective cataract surgery under peribulbar anesthesia, addition of two different doses of dexmedetomidine (25 and 50 mcg) to a mixture of 2% lidocaine (3 ml) and 0.5% bupivacaine (3 ml) shortened the onset and prolonged the duration of the block and postoperative analgesia.
The onset of corneal anesthesia and globe akinesia in their study was significantly shorter in group D50 than in the control group (P < 0.001). In group D25, the onset of corneal anesthesia was significantly shorter than in the control group but not the globe akinesia (P = 0.45). In our study we found that the onset of corneal anesthesia and globe akinesia in group D50 was significantly shorter than in the control group (1.05 ± 0.50 and 6.90 ± 1.94 vs. 1.68 ± 0.78 and 9.10 ± 2.14; P < 0.01). The onset of corneal anesthesia and globe akinesia in group D25 was shorter than in the control group (1.35 ± 0.58 and 8.13 ± 2.10), although the difference was statistically insignificant.
In the study by Channabasappa, the duration of corneal anesthesia and globe akinesia was significantly longer in groups D50 and D25 compared with the control group (P < 0.001). In our study, the duration of corneal anesthesia was significantly longer in group D50 compared with groups D25 and group C (390.40 ± 10.31, 164.41 ± 13.80, and 154.33 ± 17.34, respectively; P < 0.001). The duration of globe akinesia in group D50 was also significantly longer than in groups D25 and C (283.10 ± 26.40, 197.30 ± 25.95, and 171.00 ± 24.66, respectively; P < 0.001).
In a study that evaluated the effect of adding 100 mcg of dexmedetomidine to levobupivacaine for axillary brachial plexus blockade, it was found that dexmedetomidine shortened the onset (P < 0.05) and prolonged the duration of the block (P < 0.01) and the duration of postoperative analgesia (P < 0.05) compared with levobupivacaine alone .
Although a previous study using 100 mcg (1 ml) clonidine (a centrally acting α2 -agonist) in addition to 7 ml of 1% lidocaine concluded that clonidine did not alter, in any appreciable way, the perioperative course for patients undergoing cataract surgery , other studies have shown its beneficial effects in peribulbar block [6,16].
The exact mechanism by which α2 -adrenergic receptor agonists produce analgesia and sedation is not fully understood but is likely to be multifactorial. Peripherally, α2 -agonists reduce the release of norepinephrine and cause α2 receptor-independent inhibitory effects on nerve fiber action potentials. Centrally, α2 -agonists produce inhibit substance P release in the nociceptive pathway at the level of the dorsal root neuron and activate α2 adrenoceptors in the locus coeruleus [17,18].
In this study, we found that addition of dexmedetomidine to the local anesthetic mixture (groups D25 and D50) caused a significant decrease in IOP compared with the control group at 1, 5, and 10 min after injection (P < 0.001).
These results are similar to those obtained by Channabasappa et al. . Madan et al.  also found a similar result when they added clonidine to lidocaine during cataract surgery performed under peribulbar block.
The effect of dexmedetomidine on IOP may be due to its direct vasoconstrictor effect on afferent blood vessels of the ciliary body. This leads to reduction in aqueous humor production . It may also facilitate drainage of aqueous humor by reducing the sympathetic-mediated vasomotor tone of the ocular drainage system . Also, the hemodynamic effects of dexmedetomidine may play a role in the reduction of IOP .
Dexmedetomidine may lead to side effects such as hypotension, bradycardia, and sedation, along with anxiolysis . In this study, although the HR was lower in the D50 group than in the control group, this was found to be statistically insignificant and atropine was not needed. Mean arterial blood pressure was significantly lower in group D25 at 15 min after the block and in group D50 during the first 60 min after injection; however, this did not necessitate medical intervention.
Bradycardia was also reported with the use of dexmedetomidine in peribulbar block by Channabasappa et al.  during the first 60 min after injection, which necessitated the use of atropine (0.3 mg) in six patients of group D50 (P = 0.032), together with low arterial blood pressure for up to 30 min after injection (P = 0.049) with no pharmacological intervention.
Esmaoglu et al.  reported significant bradycardia and hypotension with the addition of dexmedetomidine to levobupivacaine for axillary block with a P-value of less than 0.05 in both. Seven patients in their study received atropine.
In this study, RSS was found to be significantly higher in groups D25 and D50 during the first 60 min following injection compared with the control group (P-values: <0.001, <0.001, 0.002, and <0.001 at 15, 30, 45, and 60 min after injection). RSS in group D50 was significantly higher than in group D25 at 45 and 60 min after injection (P < 0.05). However, these sedation scores allowed full patient cooperation.
Similar results were obtained by Channabasappa et al. . In their study RSS was significantly higher in group D50 than in the control group during the first 60 min after injection. In group D25, RSS was significantly higher than in group C for the first 20 min after injection .
In this study, time to first rescue analgesia was significantly higher in groups D25 and D50 compared with the control group (P < 0.001). The number of patients not requiring analgesia in groups D25 and D50 was higher than in the control group, although statistically nonsignificant [13 (65%), 16 (84.2%) compared with 11 (57.9%), P = 0.464]. The same was with the number of patients reporting no pain [group C: 57.9%, group D25: 85% and group D50: 94.7%, P = 0.071]. Patient and surgeon satisfaction was also higher in groups D25 and D50 than in the control group without statistical significance (P = 0.308 and 0.413, respectively).
Channabasappa et al.  also found statistically significant longer duration of analgesia in groups D50 and D25 (323.2 ± 79.57 and 251.2 ± 1.72, respectively) compared with the control group (187.2 ± 51.7). Also, total paracetamol requirement was significantly lower in D50 and D25 (0.56 ± 0.4 and 0.79 ± 0.4, respectively) compared with the control group (1.57 ± 0.92). The percentage of patients reporting no pain was higher in group D50 at 1, 6, and 24 h (96, 93, and 86%) and in group D25 (93, 73, and 76%) compared with the control group (60, 40, and 56%). In the first postoperative day, 86% of group D50, 66% of group D25, and 56% of group C did not need pain medication. This was found to be statistically significant.
Madan et al.  also reported significantly longer duration of analgesia with the addition of clonidine (1 and 1.5 mcg/kg) to a mixture of 2% lidocaine and 16 IU/ml hyaluronidase (340 ± 32 and 352 ± 22, respectively) compared with the control group (188 ± 24). The percentage of patients who were comfortable intraoperatively and postoperatively was significantly higher in clonidine 1 and 1.5 groups compared with the control group (80, 93 vs. 53% intraoperatively and 73, 80 vs. 47% postoperatively).
In our study we used levobupivacaine because of its lower myocardial and central nervous system depressant effect, superior pharmacokinetic profile, scarce reports of toxicity, and minimal treatment required to reverse toxicity with no fatal outcome . We used 0.5% concentration, which has been used safely by a number of previous studies [23-25]. However, the use of such a potent local anesthetic that provides reliable dense anesthesia might have affected the accurate detection of the effect of dexmedetomidine. However, we used them in conjunction to ensure adequate block and patient comfort during such a long surgery.
Our results have shown that addition of 50 mcg of dexmedetomidine to levobupivacaine/hyaluronidase mixture significantly shortened the onset and prolonged the duration of peribulbar block in patients undergoing vitreoretinal surgery. It also lowered the IOP and provided sedation with patient cooperation, leading to better patient and surgeon satisfaction. Addition of 25 mcg of dexmedetomidine to the same mixture caused similar effects with less significant effect on the onset of the block and more hemodynamic stability.
| Acknowledgements|| |
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table 3], [Table 4]